AAN: Rituximab Effective in Myasthenia Gravis
By John Gever, Senior Editor, MedPage Today
Published: April 14, 2010
TORONTO -- Rituximab (Rituxan), the anti-CD20 antibody that decreases B-cell activation, slashed autoantibody titers and improved symptoms in patients with myasthenia gravis (MG) refractory to standard therapies, a researcher said here.
Thirteen MG patients whose disease was not well controlled with moderate steroid doses were able to do better symptomatically and could reduce conventional treatments when rituximab was added to their therapy, reported Richard Nowak, MD, of Yale University.
In a poster presentation here at the American Academy of Neurology's annual meeting, Nowak said rituximab could become a first-line therapy for MG.
The disease results from autoantibodies against acetylcholine receptor (AChR) proteins, resulting in rapid-onset fatigue and weakness of facial and limb muscles.
Standard treatments, which most patients in this retrospective case series were receiving, include oral prednisone and plasma exchange.
Because rituximab targets antibody-producing B cells and has been used successfully in rheumatoid arthritis and some other autoimmune diseases, it seemed like a logical drug to try in MG, which Nowak called "the prototypical autoimmune disorder."
Patients in the study were considered to have refractory disease because immunotherapy could not be reduced without causing relapse, they had persistent symptoms despite conventional therapy, or they could not tolerate such treatments.
Thirteen of the 14 patients were on oral prednisone prior to starting rituximab, and twelve had undergone plasma exchange.
At the time of data analysis, five of the 13 steroid-treated patients had received one four-week cycle of 375 mg/m2 of rituximab weekly, one patient had been given two cycles, and seven had received three or more cycles.
Six of the patients stopped prednisone altogether, and six others could take a dose reduction without losing symptom control, Nowak reported. Relative to baseline, the mean reduction in steroid dose among all 13 patients was 74.9% (P=0.0009).
Among the 12 patients who had undergone plasma exchanges, most were able to stop the sessions and they were reduced in all of them. However, follow-up data beyond six months after starting rituximab were not available for four of the patients.
Titers of anti-AChR antibodies were reduced by a mean of 51.6% (P=0.0123) in six patients in whom these were measured. (Titers were not measured in patients with a different type of MG autoantibody, against the muscle specific kinase [MuSK] protein, because no commercial assay was available.)
Although the drug was given openly and the study included no control group, Nowak argued that the decline in antibody titers indicated that the improvements were not a placebo effect.
Nowak said he believed rituximab could become a first-line therapy for MG, though a prospective, controlled study would be necessary to confirm it. He said he was now trying to put one together.
A spokeswoman for Genentech, rituximab's manufacturer, said the company had no development plans in this area.
Jonathan Pincus, MD, a neurologist at Georgetown University in Washington, noted that the other alternatives to steroids, such as plasma exchange and intravenous immunoglobulin, "are expensive and carry a little bit of risk, and they can stop working. You can't use them anymore. Then you're back to where we were in the old days," when, he recalled, MG was "a serious, terrible disease."
Rituximab would clearly be an attractive alternative, he suggested.
But Pincus, who was not involved with the study, said it was unclear whether all the patients actually had CD20-positive B cells, which is the specific target for rituximab.
"That bothers me a little bit," he said. "If it's true that it works in somebody who didn't have the CD20 antigen, it's got to have some other mechanism of action, and no one has ever described that."
Nowak cited the retrospective, open-label nature of the study and the lack of antibody measurements in patients with anti-MuSK antibodies as limitations to the analysis.